Treatment of multiple brain metastases with a divide-and-conquer spatial fractionation radiosurgery approach

Brain metastases are a common problem, managed with surgery, stereotactic radiosurgery (SRS), whole brain irradiation (WBI), or a combination. SRS targets individual tumors with large dosages of radiation. There is a trend toward using more SRS and less WBI, due to a reduction in cognitive damage, shorter treatment course, and improved tumor control. In conventional radiation a total dose of radiation is frequently divided over time into several smaller "fractions", which helps spare normal tissues such as the brain. Two doses of 10 Gy each given on separate days will result in 45% less damage to normal brain tissue than a single dose of 20 Gy, according to the linear quadratic model for biologically effective dose (BED). Unfortunately, standard fractionation also reduces the effective dose to the tumor. It would therefore be highly beneficial to be able to fractionate the dose to the normal brain, but not fractionate the tumor dose. When a tumor is irradiated, there are dozens of beams that pass through the skull and converge on the tumor, also irradiating healthy brain tissue in the beam paths. If multiple tumors are irradiated, there are areas of brain that are overlapped by beams that are targeting separate tumors. If these tumors were treated on separate days, then on any given day portions of normal brain may only see the radiation beams for one tumor instead of 2 or more. That is how spatial fractionation of multiple metastases works. By treating groups of tumors on separate days the beams are spread out over time, reducing areas of beam overlap, and effectively fractionating the dose to healthy brain. Yet, each tumor still receives a single treatment. The hypothesis is that an array of metastases may be divided into 2-5 different groups that are treated on different days such that the BED to normal brain tissue is minimized. This should benefit patients by reducing side effects, allowing greater numbers of tumors to be treated, and making retreatment safer. An algorithm is discussed, which places the largest tumors and tumors situated close together into different groups. Modifications for axial beam delivery systems such as helical tomotherapy are discussed.